Synthetic tissues and vascular grafts are commercially available and have generally been made of polyethylene teraphthlate (PET), expanded polytetrafluroethylene and decellurized pericardium, and from harvested veins and arteries; they have also been constructed from naturally occurring molecules, such as collagens, elastins, chondritans and hyaluronins. However, more recently, efforts have been made to grow such graft materials, such as patches and vascular grafts, from cell cultures with varying degrees of success. U.S. Pat. No. 6,416,995 (Jul. 9, 2002), the disclosure of which is incorporated herein by reference, taught the creation of vascular grafts by recellularizing devitalized tissue materials by repopulating same in a bioreactor, using what is sometimes identified as a “constructionist” approach. It was pointed out that prior observations had suggested that the incubation of fibroblastic cells along with cardiovascular tissues should result in successful cellular penetration into the matrix structure, although some inducement might be required.
It had earlier been shown that red blood cells suspended in hyaluronic acid solutions will, when subjected to oscillating flow, readily orient and deform in the direction of flow (see More R B, Red Blood Cell Deformation in Oscillatory Flow, Thesis, University of Texas at Austin, 1997). Similar flow orientational phenomena occur in suspensions of ellipsoidal particles, rod-like particles (see Jeffery G B, The Motion of Ellipsoidal Particles Immersed in a Viscous Fluid, Proc Roy Soc, 1923; A102:161-175) and fluid droplets in emulsions (see Taylor G I, The Formation of Emulsions in Definable Fields of Flow, Proc Roy Soc, 1934; A146:501-523). Moreover, it is felt that this shear stress-deformation phenomena is ubiquitous to all cells, and thus is applicable to endothelial cells, fibroblasts and osteocytes.
U.S. Pat. No. 5,792,603 describes a bioreactor and a method for seeding and culturing a vascular graft where alternating pressure is applied to a support structure, e.g. a radial sheer stress is applied to a scaffold designed to create a vascular graft. Such techniques are believed to more effectively grow cells and tissue if such are adapted to the physical environment in which they find themselves, and thus it is believed that creating physiological flows and stresses can provide important components in defining ultimate tissue configuration. Accordingly, it is believed worthwhile to apply flows and stresses of the type that will be expected to be encountered in the proposed end use environment so that engineered tissue can be grown and cultured in a manner that will provide such with the best ultimate structure. This concept is also recognized in U.S. Pat. No. 5,928,945 (Jul. 27, 1999) where tissue-engineered cartilage was produced, the disclosure of which is also incorporated by reference; a sheer flow stress was used to grow artificial cartilage on an artificial substrate in a bioreactor.
As illustrated in these patents, such tissue engineering processes have involved the use of the pumps and circulating flow systems, e.g., where a reservoir of growth media feeds a circulating pump which maintains a constant flow through a growth chamber, as described in the '945 patent. In the '995 patent, peristaltic pumps supply solutions to a bioreactor, and pulsative flows are achieved using a pulsatile pump. While such systems have demonstrated the validity of the premise of achieving improved growth of tissue grafts through the use of shear flows and stresses, simpler systems have continued to be sought.